Resin vs. Amorolfine vs. Terbinafine Treatment in Onychomycosis
Device: Resin Lacquer
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
|Official Title:||Efficacy of Topical Resin Lacquer, Amorolfine, and Oral Terbinafine for Treating Toenail Onychomycosis: a Prospective, Randomized, Controlled, Investigator-blinded, Parallel-group Clinical Trial|
- Mycological Cure [ Time Frame: At 4- and 10 months time-points from the beginning of the study. ] [ Designated as safety issue: No ]To analyze the rate of complete mycological cure i.e. fungal eradication in terms of negative mycological culture AND negative potassium hydroxide (KOH) stain at 4- and 10 months time-points from the beginning of the study.
- Clinical Responses to the Treatments [ Time Frame: At 4- and 10 months time-points from the beginning of the study. ] [ Designated as safety issue: No ]Clinical responses to treatment were based on the proximal linear growth of healthy nail; thus, the clinical responses were classified as partial (evident proximal linear growth of healthy nail) or complete. Partial responses were defined as significant reductions in onycholysis, subungual hyperkeratosis, and streaks. A complete response was a fully normal appearance of the toenail.
- Cost-effectiveness 1 [ Time Frame: At 10-month time-point ] [ Designated as safety issue: No ]Cost analysis was based on the retail price (€) and consumption of a 10 ml bottle of Abicin® 30% resin lacquer, a 5 ml bottle of Loceryl® 5% amorolfine lacquer, and 98 tablets of generic 250 mg terbinafine, sold by the University Pharmacy in Helsinki, Finland, January 2014. The cost was expressed as the average treatment cost per patient; for the total cost, this average was extrapolated to the entire study treatment arm. The results show the treatment costs (€) per day per patient in each group.
- Cost-effectiveness 2 [ Time Frame: At 10-month time-point ] [ Designated as safety issue: No ]Cost analysis was based on the retail price (€) and consumption of a 10 ml bottle of Abicin® 30% resin lacquer, a 5 ml bottle of Loceryl® 5% amorolfine lacquer, and 98 tablets of generic 250 mg terbinafine, sold by the University Pharmacy in Helsinki, Finland, January 2014. The cost was expressed as the average treatment cost per patient; for the total cost, this average was extrapolated to the entire study treatment arm. The results show the treatment costs (€) during the treatment period per patient in each group.
- Compliance to the Treatment [ Time Frame: At 4-month time-point ] [ Designated as safety issue: No ]Evaluation of compliance was based on patient self-reports of whether the treatment protocol was followed 100% (complete), 80% (good), 60% (moderate), or 40% (poor) of the time.
|Study Start Date:||October 2013|
|Study Completion Date:||October 2014|
|Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: Resin Lacquer
Topical 30% Resin Lacquer applied once daily for 9 months (Abicin® 30% Nail Lacquer).
Device: Resin Lacquer
30% Resin Lacquer is applied once daily for 9 months (Abicin®) in toenail onychomycosis.
Other Name: Resin Lacquer arm
Active Comparator: Amorolfine
Topical 5% Amorolfine Lacquer applied once weekly for 9 months (Loceryl® 5% Nail Lacquer).
5% Amorolfine Lacquer is applied once weekly for 9 months (Loceryl®) in toenail onychomycosis.
Other Name: Amorolfine Lacquer arm
Active Comparator: Terbinafine
250 mg of Terbinafine taken orally once daily for 3 months (Generics).
250 mg of Terbinafine is taken orally once daily for 3 months (Generics) in toenail onychomycosis.
Other Name: Terbinafine arm
The aim of this prospective, investigator-blinded, randomized and controlled clinical trial is to explore potential differences between 5 % amorolfine and 30 % resin lacquer in topical treatment of onychomycosis. In addition, topical treatment methods are compared with the most effective 'drug of choice' for onychomycosis according the current guidelines i.e. oral medication with terbinafine.
Altogether 90 patients (the aim is to collect the 30 patients per group) who have culture or potassium hydroxide (KOH) stain verified dermatophyte onychomycosis are randomly allocated into 3 treatment groups to receive either topical treatment or oral medication for toenail onychomycosis classified as follows:
- White superficial onychomycosis (WSO)
- Distal and lateral subungual onychomycosis (DLSO)
- Proximal subungual onychomycosis (PSO)
- [Total dystrophic onychomycosis) (TDO)] [Excluded]
- [Candidal onychomycosis] [Excluded]
Participants are randomized into 3 groups to receive:
- Topical treatment: 30 % resin lacquer (Abicin®) applied once daily for 9 months.
- Topical treatment: 5 % amorolfine lacquer (Loceryl®) applied once weekly for 9 months.
- Oral medication: 250 mg terbinafine taken orally once daily for 3 months.
All patients visit at outpatient department before the launch of the study, and 3 and 9 months thereafter. Clinical examination is done by 4 physicians. During the 42-week study period, laboratory tests are conducted on samples collected before treatment, at 20 weeks, and at 42 weeks. The tests include a fungal culture, KOH staining of the toenail sample, and blood tests. Cultures and KOH microscopy are performed in an independent, specialised mycology laboratory with standard techniques (Medix Laboratories Ltd., Helsinki, Finland). The blood tests measure plasma γ-glutamyl transferase levels (also at 2 weeks); plasma creatinine levels; the total number of white blood cells, including neutrophils, monocytes, basophils, lymphocytes, and eosinophils; the total number of red blood cells, including erythrocytes and haematocrit; erythrocyte indices, including the mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, and haemoglobin level; and the total number thrombocytes (initially and at 42 weeks). During the control visits, sequential digital photographs of the most disfigured and brittle toenails are acquired.
In the three phone calls, patients are asked about potential treatment-related side effects, compliance with treatment, patients' perception of treatment outcome, and their willingness to continue in the study. In each treatment arm, the treatment regimen is discontinued 5 weeks before the last toenail sampling to provide an appropriate washout period before the final culture and KOH analysis.
To ensure safety and to assess potential contraindications for the treatment regimens, all patients included in the study undergo a comprehensive medical interview and physical examination. To identify patients who may develop intolerable adverse events due to drug combinations, all concurrent medications are cross-checked to verify compatibility with resin, amorolfine, and terbinafine regimens at the beginning of the study. All patients are informed of the possibility of developing a hypersensitivity to resin, amorolfine, or terbinafine. If patients experienced symptoms that corresponded to any level of hypersensitivity, they are dropped from the study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01851590
|Vääksy, Finland, FI-17200|
|Principal Investigator:||Janne J. Jokinen, MD, PhD||Department of Cardiac Surgery, Heart and Lung Centre, Helsinki University Hospital, FI-00029, Helsinki, Finland|